title: Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults.
abstract: T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that programmed death-1 (PD-1) regulates T cell dysfunction during chronic lymphocytic choriomeningitis virus infection in mice, and PD-1(hi) cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, hepatitis C virus, and hepatitis B virus. However, it is not known if PD-1(hi) cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1(hi) versus PD-1(lo) CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1(hi) CD8 T cells in healthy humans did not significantly correlate with the PD-1(hi) exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. In conclusion, our study shows that most PD-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells.
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jaikumar
authors.initials: J
authors.lastname: Duraiswamy
authors.forename: Chris C
authors.initials: CC
authors.lastname: Ibegbu
authors.forename: David
authors.initials: D
authors.lastname: Masopust
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Miller
authors.forename: Koichi
authors.initials: K
authors.lastname: Araki
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Doho
authors.forename: Pramila
authors.initials: P
authors.lastname: Tata
authors.forename: Satish
authors.initials: S
authors.lastname: Gupta
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zilliox
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.forename: W Nicholas
authors.initials: WN
authors.lastname: Haining
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count / Q000379:methods; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D061026:Programmed Cell Death 1 Receptor; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor